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Study Comparing Efficacy and Safety of Defibrotide vs Best Supportive Care in the Prevention of Hepatic Veno-Occlusive Disease in Adult and Pediatric Patients

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ClinicalTrials.gov Identifier: NCT02851407
Recruitment Status : Completed
First Posted : August 1, 2016
Results First Posted : March 2, 2022
Last Update Posted : March 2, 2022
Sponsor:
Information provided by (Responsible Party):
Jazz Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Condition Veno-occlusive Disease
Interventions Drug: Defibrotide
Other: Best Supportive Care
Enrollment 372
Recruitment Details  
Pre-assignment Details Participants, their parents/legal guardians, or representatives were required to sign a statement of informed consent.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT. Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Period Title: Overall Study
Started 190 182
Completed 120 121
Not Completed 70 61
Reason Not Completed
Withdrawal by parent/guardian             2             7
Protocol deviation             0             1
Transferred to another hospital to continue             1             0
Other Death             30             20
Adverse event, serious fatal             6             8
Consent withdrawn by participant             5             3
Screen failure             2             1
Disease relapse             9             6
Physician Decision             7             6
Transferred to hospital closer to home             0             1
Enrolled in an investigational study             0             1
Early recovery             1             0
Adverse event, non-fatal             7             5
Lost to Follow-up             0             2
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care Total
Hide Arm/Group Description Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.

Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.

Best Supportive Care

Total of all reporting groups
Overall Number of Baseline Participants 190 182 372
Hide Baseline Analysis Population Description
Baseline characteristics were assessed using the Intent-to-Treat Analysis Set.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 190 participants 182 participants 372 participants
22.7  (21.87) 23.2  (21.73) 23.0  (21.77)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 190 participants 182 participants 372 participants
Participants ≤16 Years
104
  54.7%
94
  51.6%
198
  53.2%
Participants >16 Years
86
  45.3%
88
  48.4%
174
  46.8%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 190 participants 182 participants 372 participants
Female
90
  47.4%
82
  45.1%
172
  46.2%
Male
100
  52.6%
100
  54.9%
200
  53.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 190 participants 182 participants 372 participants
Hispanic or Latino
22
  11.6%
21
  11.5%
43
  11.6%
Not Hispanic or Latino
150
  78.9%
143
  78.6%
293
  78.8%
Unknown or Not Reported
18
   9.5%
18
   9.9%
36
   9.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 190 participants 182 participants 372 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
39
  20.5%
46
  25.3%
85
  22.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
2
   1.1%
2
   0.5%
Black or African American
5
   2.6%
8
   4.4%
13
   3.5%
White
125
  65.8%
109
  59.9%
234
  62.9%
More than one race
2
   1.1%
0
   0.0%
2
   0.5%
Unknown or Not Reported
19
  10.0%
17
   9.3%
36
   9.7%
1.Primary Outcome
Title Veno-occlusive Disease (VOD)-Free Survival by Day +30 Post-Hematopoietic Stem Cell Transplant (HSCT) Per the Independent Endpoint Adjudication Committee (EPAC)
Hide Description VOD-free survival is a composite of survival status and VOD occurrence as determined by modified Seattle criteria adjudicated by a blinded independent EPAC. An event is defined as a VOD diagnosis (as assessed by the EPAC) or death, whichever, is earlier, up to and including Day +30 post-HSCT. The values reported below are participants who did not experience VOD or death by Day +30 post-HSCT.
Time Frame Day +30 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
VOD-free survival was assessed using the Intent-to-Treat Analysis Set.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 190 182
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: KM Estimate % of participants
66.8
(57.8 to 74.4)
72.5
(62.3 to 80.4)
2.Secondary Outcome
Title Veno-Occlusive Disease (VOD)-Free Survival by Day +100 Post-Hematopoietic Stem Cell Transplant (HSCT) Per the Independent Endpoint Adjudication Committee (EPAC)
Hide Description VOD-free survival is a composite of survival status and VOD occurrence as determined by modified Seattle criteria adjudicated by a blinded independent EPAC. An event is defined as a VOD diagnosis (as assessed by the EPAC) or death, whichever, is earlier, up to and including Day +100 post-HSCT. The values reported below are participants who did not experience VOD or death by Day +100 post-HSCT.
Time Frame Day +100 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
VOD-free survival was assessed using the Intent-to-Treat Analysis Set.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 190 182
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: KM Estimate % of participants
49.8
(26.1 to 69.5)
57.1
(36.6 to 73.1)
3.Secondary Outcome
Title Percentage of Participants With Veno-Occlusive Disease (VOD) by Day +30 Post-Hematopoietic Stem Cell Transplant (HSCT)
Hide Description The number of participants who were diagnosed with VOD based on the Modified Seattle Criteria as per blinded EPAC assessment. The percentage was calculated out of the total number of participants in each arm of the study. The values reported below are the numbers and percentages of participants who experienced VOD by Day +30 post-HSCT.
Time Frame Day +30 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
Percentage of Participants with VOD by Day +30 post-HSCT was assessed using the Intent-to-Treat Analysis Set.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 190 182
Measure Type: Count of Participants
Unit of Measure: Participants
47
  24.7%
38
  20.9%
4.Secondary Outcome
Title Veno-Occlusive Disease (VOD)-Free Survival Rate by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)
Hide Description VOD-free survival is a composite of survival status and VOD occurrence as determined by modified Seattle criteria. An event is defined as a VOD diagnosis or death, whichever, is earlier, up to and including Day +180 post-HSCT. The diagnosis of VOD through Day +100 post-HSCT was based on Endpoint Adjudication Committee (EPAC), and the diagnosis of VOD after Day +100 post-HSCT was based on investigator assessments. The values reported below are participants who did not experience VOD or death by Day +180 post-HSCT.
Time Frame Day +180 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
VOD-free Survival by Day +180 post-HSCT was assessed using the Intent-to-Treat Analysis Set.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 190 182
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: KM Estimate % of participants
34.6
(18.2 to 51.8)
42.8
(26.7 to 58.0)
5.Secondary Outcome
Title Non-Relapse Mortality (NRM) for Defibrotide (DP) and Best Supportive Care (BSC) by Days +100 and +180 Post-Hematopoietic Stem Cell Transplant (HSCT)
Hide Description NRM is defined as death that occurs after HSCT in participants who were noted as having malignant primary disease on the disease history electronic case report form (eCRF) and do not have primary disease relapse post-HSCT.
Time Frame Days +100 and +180 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
Non-relapse mortality was assessed using the number of participants with malignant primary disease within treatment arm from the Intent-to-Treat Analysis Set.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 147 139
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: KM Estimate % of non-relapse survival
Day +100 Post-HSCT
80.4
(71.6 to 86.8)
89.7
(82.1 to 94.2)
Day +180 Post-HSCT
77.9
(68.4 to 84.9)
81.9
(70.8 to 89.1)
6.Secondary Outcome
Title Percentage of Participants With Veno-Occlusive Disease (VOD)-Associated Multi-Organ Dysfunction (MOD) by Days +30 and Days +100 Post-Hematopoietic Stem Cell Transplant (HSCT) in Patients Who Developed VOD
Hide Description VOD-associated MOD is defined for participants as occurring if the investigator answers "Yes" to the question "Has the participant been diagnosed with VOD associated MOD?" in the electronic case report form (eCRF). The values below are the number of participants who received the answer, "Yes."
Time Frame Days +30 and +100 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
Percentage of Participants with VOD-associated MOD was assessed using the Intent-to-Treat Analysis Set.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 190 182
Measure Type: Count of Participants
Unit of Measure: Participants
Day +30 Post-HSCT
8
   4.2%
8
   4.4%
Day +100 Post-HSCT
9
   4.7%
10
   5.5%
7.Secondary Outcome
Title Percentage of Participants Who Had Resolution of Veno-Occlusive Disease (VOD) by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)
Hide Description The proportion of participants who had resolution of VOD by Day +180 post-HSCT is reported as a percentage.
Time Frame Day +180 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
Resolution of VOD was assessed using the Intent-To-Treat Analysis Set. The overall number analyzed is the number of participants diagnosed with VOD by Day +30 post-HSCT by the investigator.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 23 29
Measure Type: Count of Participants
Unit of Measure: Participants
6
  26.1%
15
  51.7%
8.Secondary Outcome
Title Time to Resolution of Veno-Occlusive Disease (VOD) by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)
Hide Description Time to Resolution of VOD is calculated as follows: Time to Resolution of VOD= [Date of VOD resolution] - [Date of VOD diagnosis by investigator].
Time Frame Day +180 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
Resolution of VOD was assessed using the Intent-To-Treat Analysis.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 190 182
Median (95% Confidence Interval)
Unit of Measure: Days
NA [1] 
(NA to NA)
30.0
(21.0 to 48.0)
[1]
Not assessable. There were not enough participants who had VOD resolution for this to be estimated. The value is not estimable because the number of VOD resolution, i.e 6, is less than half of the number of diagnosed VOD in the DP arm, so the KM estimate of median time cannot be evaluated.
9.Secondary Outcome
Title Percentage of Participants With Veno-Occlusive Disease (VOD) After Day +30 Post-Hematopoietic Stem Cell Transplant (HSCT) up to Days +100 and +180 Post-HSCT
Hide Description The values shown are the number and percentage of participants with VOD after day +30 post-HSCT and on or before Days +100 and +180 post-HSCT. The diagnosis of VOD through Day +100 post-HSCT was made by Endpoint Adjudication Committee (EPAC), and the diagnosis of VOD after Day +100 post-HSCT was based on investigator assessments.
Time Frame Days +100 and +180 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
Percentage of VOD was assessed using the Intent-to-Treat Analysis Set.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 190 182
Measure Type: Count of Participants
Unit of Measure: Participants
Day +100 Post-HSCT
6
   3.2%
5
   2.7%
Day +180 Post-HSCT
6
   3.2%
5
   2.7%
10.Secondary Outcome
Title Change in 5-Level EuroQol-5D (EQ-5D-5L) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Adult Participants Age ≥ 16 Years: Mobility
Hide Description For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-5L, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 Post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.
Time Frame Day +180 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
EQ-5D-5L Mobility was assessed using the Age ≥ 16 Years Safety Analysis Set.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 45 46
Measure Type: Count of Participants
Unit of Measure: Participants
Condition improved
4
   8.9%
7
  15.2%
Condition unchaged
28
  62.2%
28
  60.9%
Condition deteriorated
9
  20.0%
6
  13.0%
Unknown
4
   8.9%
5
  10.9%
11.Secondary Outcome
Title Change in 5-Level EuroQol-5D (EQ-5D-5L) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Adult Participants Age ≥ 16 Years: Self-Care
Hide Description For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-5L, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 Post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.
Time Frame Day +180 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
EQ-5D-5L Self-Care was assessed using the Age ≥ 16 Years Safety Analysis Set.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 45 46
Measure Type: Count of Participants
Unit of Measure: Participants
Condition improved
3
   6.7%
6
  13.0%
Condition unchaged
35
  77.8%
32
  69.6%
Condition deteriorated
3
   6.7%
4
   8.7%
Unknown
4
   8.9%
4
   8.7%
12.Secondary Outcome
Title Change in 5-Level EuroQol-5D (EQ-5D-5L) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Adult Participants Age ≥ 16 Years: Activity
Hide Description For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-5L, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 Post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.
Time Frame Day +180 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
EQ-5D-5L Activity was assessed using the Age ≥ 16 Years Safety Analysis Set.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 45 46
Measure Type: Count of Participants
Unit of Measure: Participants
Condition improved
7
  15.6%
10
  21.7%
Condition unchaged
24
  53.3%
22
  47.8%
Condition deteriorated
9
  20.0%
10
  21.7%
Unknown
5
  11.1%
4
   8.7%
13.Secondary Outcome
Title Change in 5-Level EuroQol-5D (EQ-5D-5L) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Adult Participants Age ≥ 16 Years: Pain
Hide Description For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-5L, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 Post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.
Time Frame Day +180 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
EQ-5D-5L Pain was assessed using the Age ≥ 16 Years Safety Analysis Set.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 45 46
Measure Type: Count of Participants
Unit of Measure: Participants
Condition improved
10
  22.2%
11
  23.9%
Condition unchaged
25
  55.6%
19
  41.3%
Condition deteriorated
6
  13.3%
12
  26.1%
Unknown
4
   8.9%
4
   8.7%
14.Secondary Outcome
Title Change in 5-Level EuroQol-5D (EQ-5D-5L) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Adult Participants Age ≥ 16 Years: Anxiety
Hide Description For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-5L, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 Post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.
Time Frame Day +180 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
EQ-5D-5L Anxiety was assessed using the Age ≥ 16 Years Safety Analysis Set.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 45 46
Measure Type: Count of Participants
Unit of Measure: Participants
Condition improved
11
  24.4%
11
  23.9%
Condition unchaged
22
  48.9%
27
  58.7%
Condition deteriorated
7
  15.6%
4
   8.7%
Unknown
5
  11.1%
4
   8.7%
15.Secondary Outcome
Title Change in EuroQol-5D for Youth (EQ-5D-Y) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Pediatric Participants Age ≥ 4 and ≤ 7 Years: Mobility
Hide Description For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-Y, self-report version, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.
Time Frame Day +180 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
EQ-5D-Y Mobility was assessed using the Age ≥ 4 and ≤ 7 Years Safety Analysis Set.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 15 15
Measure Type: Count of Participants
Unit of Measure: Participants
Condition improved
2
  13.3%
1
   6.7%
Condition unchanged
8
  53.3%
8
  53.3%
Condition deteriorated
3
  20.0%
4
  26.7%
Unknown
2
  13.3%
2
  13.3%
16.Secondary Outcome
Title Change in EuroQol-5D for Youth (EQ-5D-Y) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Pediatric Participants Age ≥ 4 and ≤ 7 Years: Self-Care
Hide Description For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-Y, self-report version, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.
Time Frame Day +180 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
EQ-5D-Y Self-Care was assessed using the Age ≥ 4 and ≤ 7 Years Safety Analysis Set.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 15 15
Measure Type: Count of Participants
Unit of Measure: Participants
Condition improved
3
  20.0%
2
  13.3%
Condition unchanged
7
  46.7%
10
  66.7%
Condition deteriorated
3
  20.0%
1
   6.7%
Unknown
2
  13.3%
2
  13.3%
17.Secondary Outcome
Title Change in EuroQol-5D for Youth (EQ-5D-Y) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Pediatric Participants Age ≥ 4 and ≤ 7 Years: Activity
Hide Description For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-Y, self-report version, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.
Time Frame Day +180 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
EQ-5D-Y Activity was assessed using the Age ≥ 4 and ≤ 7 Years Safety Analysis Set.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 15 15
Measure Type: Count of Participants
Unit of Measure: Participants
Condition improved
2
  13.3%
1
   6.7%
Condition unchanged
7
  46.7%
11
  73.3%
Condition deteriorated
4
  26.7%
1
   6.7%
Unknown
2
  13.3%
2
  13.3%
18.Secondary Outcome
Title Change in EuroQol-5D for Youth (EQ-5D-Y) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Pediatric Participants Age ≥ 4 and ≤ 7 Years: Pain
Hide Description For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-Y, self-report version, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.
Time Frame Day +180 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
EQ-5D-Y Pain was assessed using the Age ≥ 4 and ≤ 7 Years Safety Analysis Set.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 15 15
Measure Type: Count of Participants
Unit of Measure: Participants
Condition improved
4
  26.7%
3
  20.0%
Condition unchanged
7
  46.7%
9
  60.0%
Condition deteriorated
2
  13.3%
1
   6.7%
Unknown
2
  13.3%
2
  13.3%
19.Secondary Outcome
Title Change in EuroQol-5D for Youth (EQ-5D-Y) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Pediatric Participants Age ≥ 4 and ≤ 7 Years: Anxiety
Hide Description For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-Y, self-report version, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.
Time Frame Day +180 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
EQ-5D-Y Anxiety was assessed using the Age ≥ 4 and ≤ 7 Years Safety Analysis Set.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 15 15
Measure Type: Count of Participants
Unit of Measure: Participants
Condition improved
3
  20.0%
2
  13.3%
Condition unchanged
8
  53.3%
10
  66.7%
Condition deteriorated
2
  13.3%
1
   6.7%
Unknown
2
  13.3%
2
  13.3%
20.Secondary Outcome
Title Change in EuroQol-5D for Youth (EQ-5D-Y) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Pediatric Participants Age ≥ 8 and ≤ 15 Years: Mobility
Hide Description For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-Y, self-report version, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.
Time Frame Day +180 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
EQ-5D-Y Mobility at Day +180 post-HSCT was assessed using participants Age ≥ 8 and ≤ 15 Years Safety Analysis Set.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 14 17
Measure Type: Count of Participants
Unit of Measure: Participants
Condition improved
1
   7.1%
2
  11.8%
Condition unchanged
9
  64.3%
10
  58.8%
Condition deteriorated
3
  21.4%
4
  23.5%
unknown
1
   7.1%
1
   5.9%
21.Secondary Outcome
Title Change in EuroQol-5D for Youth (EQ-5D-Y) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Pediatric Participants Age ≥ 8 and ≤ 15 Years: Self-Care
Hide Description For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-Y, self-report version, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.
Time Frame Day +180 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
EQ-5D-Y Self-Care at Day +180 post-HSCT was assessed using participants Age ≥ 8 and ≤ 15 Years Safety Analysis Set.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 14 17
Measure Type: Count of Participants
Unit of Measure: Participants
Condition improved
3
  21.4%
4
  23.5%
Condition unchanged
8
  57.1%
10
  58.8%
Condition deteriorated
2
  14.3%
2
  11.8%
Unknown
1
   7.1%
1
   5.9%
22.Secondary Outcome
Title Change in EuroQol-5D for Youth (EQ-5D-Y) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Pediatric Participants Age ≥ 8 and ≤ 15 Years: Activity
Hide Description For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-Y, self-report version, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.
Time Frame Day +180 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
EQ-5D-Y Activity at Day +180 post-HSCT was assessed using participants Age ≥ 8 and ≤ 15 Years Safety Analysis Set.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 14 17
Measure Type: Count of Participants
Unit of Measure: Participants
Condition improved
1
   7.1%
3
  17.6%
Condition unchanged
7
  50.0%
10
  58.8%
Condition deteriorated
5
  35.7%
3
  17.6%
Unknown
1
   7.1%
1
   5.9%
23.Secondary Outcome
Title Change in EuroQol-5D for Youth (EQ-5D-Y) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Pediatric Participants Age ≥ 8 and ≤ 15 Years: Pain
Hide Description For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-Y, self-report version, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.
Time Frame Day +180 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
EQ-5D-Y Pain at Day +180 post-HSCT was assessed using participants Age ≥ 8 and ≤ 15 Years Safety Analysis Set.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 14 17
Measure Type: Count of Participants
Unit of Measure: Participants
Condition improved
0
   0.0%
5
  29.4%
Condition unchanged
12
  85.7%
8
  47.1%
Condition deteriorated
1
   7.1%
3
  17.6%
Unknown
1
   7.1%
1
   5.9%
24.Secondary Outcome
Title Change in EuroQol-5D for Youth (EQ-5D-Y) Dimensions From Baseline to Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT) for Pediatric Participants Age ≥ 8 and ≤ 15 Years: Anxiety
Hide Description For each of the five dimensions of mobility, self-care, activity, pain, and anxiety based on the descriptive system of the EQ-5D-Y, self-report version, the numbers and percentages of participants for all categories (the three levels of reported problems and question not completed) at Day +180 post-HSCT was assessed. Each dimension was categorized as follows: Condition improved, if the reported level of problem is lower at the assessment than baseline; condition unchanged, if the reported level of problem remains the same; condition deteriorated, if the reported level of problem is higher at that assessment than at baseline; and unknown, if the reported level of problem is missing either at baseline or at that assessment.
Time Frame Day +180 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
EQ-5D-Y Pain at Day +180 post-HSCT was assessed using participants Age ≥ 8 and ≤ 15 Years Safety Analysis Set.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 14 17
Measure Type: Count of Participants
Unit of Measure: Participants
Condition improved
6
  42.9%
6
  35.3%
Condition unchanged
5
  35.7%
8
  47.1%
Condition deteriorated
2
  14.3%
2
  11.8%
Unknown
1
   7.1%
1
   5.9%
25.Secondary Outcome
Title Maximum Plasma Concentration (Cmax) of Defibrotide Prophylaxis During the Prophylaxis Phase
Hide Description Cmax is the maximum defibrotide plasma concentration, obtained directly from the observed data. Cmax is a summary statistic and it is not reported on an hourly basis. If veno-occlusive disease (VOD) occurs, the prophylaxis phase starts on the baseline date and ends on the day before the start date of rescue defibrotide. If VOD does not occur, the prophylaxis phase starts on the baseline date and ends on the date of study completion/early termination.
Time Frame Day +1 and +7 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
Cmax was assessed using the Pharmacokinetic (PK) Evaluable Analysis Set. Intensive PK samples were collected during the prophylaxis phase on Day +1 and Day +7 post-HSCT in a subgroup of participants in the DP arm who separately consented for this sampling. Sparse PK samples were collected from participants throughout the study according to the protocol.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 2 0
Mean (Standard Deviation)
Unit of Measure: μg/mL
Day +1 Post-HSCT 30.4  (10.600)
Day +7 Post-HSCT 40  (3.168)
26.Secondary Outcome
Title Area Under the Defibrotide Concentration-Time Curve (AUClast) of Defibrotide Prophylaxis During the Prophylaxis Phase
Hide Description AUClast is the area under the defibrotide concentration-time curve from 0 (pre-dose) to time of last quantifiable defibrotide concentration at time "t". AUClast is a summary statistic and it is not reported on an hourly basis. If veno-occlusive disease (VOD) occurs, the prophylaxis phase starts on the baseline date and ends on the day before the start date of rescue defibrotide. If VOD does not occur, the prophylaxis phase starts on the baseline date and ends on the date of study completion/early termination.
Time Frame Day +1 and +7 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
AUClast was assessed using the Pharmacokinetic (PK) Evaluable Analysis Set. Intensive PK samples were collected during the prophylaxis phase on Day +1 and Day +7 post-HSCT in a subgroup of participants in the DP arm who separately consented for this sampling. Sparse PK samples were collected from participants throughout the study according to the protocol.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 2 0
Mean (Standard Deviation)
Unit of Measure: h*μg/mL
Day +1 Post-HSCT 61.6  (28.488)
Day +7 Post-HSCT 78.2  (10.781)
27.Secondary Outcome
Title Mean Clearance of Defibrotide Prophylaxis During the Prophylaxis Phase
Hide Description Mean systemic clearance after intravenous dosing. Mean clearance is a summary statistic and it is not reported on an hourly basis. If veno-occlusive disease (VOD) occurs, the prophylaxis phase starts on the baseline date and ends on the day before the start date of rescue defibrotide. If VOD does not occur, the prophylaxis phase starts on the baseline date and ends on the date of study completion/early termination.
Time Frame Day +1 and +7 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
Mean clearance was assessed using the Pharmacokinetic (PK) Evaluable Analysis Set. Intensive PK samples were collected during the prophylaxis phase on Day +1 and Day +7 post-HSCT in a subgroup of participants in the DP arm who separately consented for this sampling. Sparse PK samples were collected from participants throughout the study according to the protocol.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 2 0
Mean (Standard Deviation)
Unit of Measure: L/h
Day +1 Post-HSCT Number Analyzed 2 participants 0 participants
4.7  (0.304)
Day +7 Post-HSCT Number Analyzed 0 participants 0 participants
28.Secondary Outcome
Title Volume of Distribution of Defibrotide Prophylaxis During the Prophylaxis Phase
Hide Description Mean volume of distribution following intravenous dosing. Mean volume of distribution is a summary statistic and it is not reported on an hourly basis.If veno-occlusive disease (VOD) occurs, the prophylaxis phase starts on the baseline date and ends on the day before the start date of rescue defibrotide. If VOD does not occur, the prophylaxis phase starts on the baseline date and ends on the date of study completion/early termination.
Time Frame Day +1 and +7 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
Volume of distribution was assessed using the Pharmacokinetic (PK) Evaluable Analysis Set. Intensive PK samples were collected during the prophylaxis phase on Day +1 and Day +7 post-HSCT in a subgroup of participants in the DP arm who separately consented for this sampling. Sparse PK samples were collected from participants throughout the study according to the protocol.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 2 0
Mean (Standard Deviation)
Unit of Measure: L
Day +1 Post-HSCT 7.9  (0.689)
Day +7 Post-HSCT 5.9  (1.609)
29.Secondary Outcome
Title Maximum Plasma Concentration (Cmax) of Defibrotide Prophylaxis During the Rescue Phase
Hide Description Cmax is the maximum defibrotide plasma concentration, obtained directly from the observed data. Cmax is a summary statistic and it is not reported on an hourly basis. For the subset of participants who developed veno-occlusive disease (VOD) and received rescue defibrotide, the rescue treatment phase begins on the start date of rescue defibrotide and ends on the date of study completion/early termination.
Time Frame Day +14 Post-VOD Treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Cmax was assessed using the Pharmacokinetic (PK) Evaluable Analysis Set. Frequent PK samples were collected from participants who developed VOD and received defibrotide rescue treatment (rescue phase) on VOD treatment Day 14. Sparse PK samples were collected from participants throughout the study according to the protocol.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 4 14
Mean (Standard Deviation)
Unit of Measure: μg/mL
44.4  (18.550) 39.7  (25.775)
30.Secondary Outcome
Title Area Under the Defibrotide Concentration-Time Curve (AUClast) of Defibrotide Prophylaxis During the Rescue Phase
Hide Description AUClast is the area under the defibrotide concentration-time curve from 0 (pre-dose) to time of last quantifiable defibrotide concentration at time "t". AUClast is a summary statistic and it is not reported on an hourly basis. For the subset of participants who developed veno-occlusive disease (VOD) and received rescue defibrotide, the rescue treatment phase begins on the start date of rescue defibrotide and ends on the date of study completion/early termination.
Time Frame Day +14 Post-VOD Treatment
Hide Outcome Measure Data
Hide Analysis Population Description
AUClast was assessed using the Pharmacokinetic (PK) Evaluable Analysis Set. Frequent PK samples were collected from participants who developed VOD and received defibrotide rescue treatment (rescue phase) on VOD treatment Day 14. Sparse PK samples were collected from participants throughout the study according to the protocol.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 4 14
Mean (Standard Deviation)
Unit of Measure: h*μg/mL
119.1  (68.875) 90.7  (54.798)
31.Secondary Outcome
Title Volume of Distribution of Defibrotide Prophylaxis During the Rescue Phase
Hide Description Mean volume of distribution following intravenous dosing. Mean volume of distribution is a summary statistic and it is not reported on an hourly basis. For the subset of participants who developed veno-occlusive disease (VOD) and received rescue defibrotide, the rescue treatment phase begins on the start date of rescue defibrotide and ends on the date of study completion/early termination.
Time Frame Day +14 Post-VOD Treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Volume of distribution was assessed using the Pharmacokinetic (PK) Evaluable Analysis Set. Frequent PK samples were collected from participants who developed VOD and received defibrotide rescue treatment (rescue phase) on VOD treatment Day 14. Sparse PK samples were collected from participants throughout the study according to the protocol.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 2 9
Mean (Standard Deviation)
Unit of Measure: L
6.3  (0.654) 6.7  (5.895)
32.Secondary Outcome
Title Percentage of Participants With Grades 2, 3, and 4 Acute Graft-Versus-Host-Disease (GvHD) by Days +30, +100, and +180 Post-Hematopoietic Stem Cell Transplant (HSCT) in the Prophylaxis Phase
Hide Description The number and percentage of participants with Grade 2-4 acute GvHD in the prophylaxis phase. Grade 2 is defined as Skin stage = 3, or Liver stage = 1, or GI stage = 1. Grade 3 is defined as Skin stage = 3, or Liver stage = 2-3, or GI stage = 2-4. Grade 4 is defined as a Skin stage = 4, or Liver stage = 4, or GI stage = 2-4.
Time Frame Days +30, +100, and +180 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
Percentage of participants with acute GvHD was assessed using the Safety Analysis Set. Percentages were calculated with the number of participants in Safety Analysis Set who entered the study phase in each arm as a denominator during the prophylaxis phase.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 147 142
Measure Type: Count of Participants
Unit of Measure: Participants
Day +30 Post-HSCT
13
   8.8%
13
   9.2%
Day +100 Post-HSCT
20
  13.6%
24
  16.9%
Day +180 Post-HSCT
22
  15.0%
26
  18.3%
33.Secondary Outcome
Title Percentage of Participants With Grades 2, 3, and 4 Acute Graft-Versus-Host-Disease (GvHD) by Days +30, +100, and +180 Post-Hematopoietic Stem Cell Transplant (HSCT) in the Rescue Phase
Hide Description The number and percentage of participants with Grade 2-4 acute GvHD in the rescue phase. Grade 2 is defined as Skin stage = 3, or Liver stage = 1, or GI stage = 1. Grade 3 is defined as Skin stage = 3, or Liver stage = 2-3, or GI stage = 2-4. Grade 4 is defined as a Skin stage = 4, or Liver stage = 4, or GI stage = 2-4.
Time Frame Days +30, +100, and +180 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
Percentage of participants with acute GvHD was assessed using the Safety Analysis Set. Percentages were calculated with the number of participants in Safety Analysis Set who entered the study phase in each arm as a denominator during the rescue phase.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 23 28
Measure Type: Count of Participants
Unit of Measure: Participants
Day +30 Post-HSCT
5
  21.7%
1
   3.6%
Day +100 Post-HSCT
6
  26.1%
1
   3.6%
Day +180 Post-HSCT
6
  26.1%
1
   3.6%
34.Secondary Outcome
Title Percentage of Participants With Chronic Graft-Versus-Host-Disease (GvHD) by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)
Hide Description The values shown are the number and percentages of participants who developed chronic GvHD by Day +180 post-HSCT in the prophylaxis phase and rescue phase.
Time Frame Day +180 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
Percentage of participants chronic GvHD was assessed using the Safety Analysis Set. Percentages were calculated with the number of participants in Safety Analysis Set who entered the study phase in each arm as a denominator. The number analyzed differs from the overall number of participants analyzed due to the count of participants included in the prophylaxis phase versus the rescue phase.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 181 174
Measure Type: Count of Participants
Unit of Measure: Participants
Prophylaxis Phase Number Analyzed 181 participants 174 participants
14
   7.7%
12
   6.9%
Rescue Phase Number Analyzed 23 participants 28 participants
2
   8.7%
1
   3.6%
35.Secondary Outcome
Title Number of Participants With Graft Failure During the Prophylaxis Phase and Rescue Phase
Hide Description Graft failure is defined as participants that after hematopoietic stem cell transplant (HSCT) never reached an absolute neutrophil count >0.5 x 10^9/L that is maintained for three consecutive days or a platelet count >20 x 10^9/L without a platelet transfusion in the preceding seven days. If veno-occlusive disease (VOD) occurs, the prophylaxis phase starts on the baseline date and ends on the day before the start date of rescue defibrotide. If VOD does not occur, the prophylaxis phase starts on the baseline date and ends on the date of study completion/early termination. For the subset of participants who developed VOD and received rescue defibrotide, the rescue treatment phase begins on the start date of rescue defibrotide and ends on the date of study completion/early termination.
Time Frame Day +180 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants with graft failure was assessed using the Safety Analysis Set.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 181 174
Measure Type: Count of Participants
Unit of Measure: Participants
Prophylaxis Phase
4
   2.2%
5
   2.9%
Rescue Phase
4
   2.2%
4
   2.3%
36.Secondary Outcome
Title Number of Participants With Neutrophil Engraftment by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)
Hide Description The date of neutrophil engraftment was recorded on the electronic case report form (eCRF) and is defined as the first date after HSCT of an absolute neutrophil count >0.5 x 10^9/L that is maintained for three consecutive days. The definition of "absolute neutrophil count" includes both segmented neutrophils and "bands," immature neutrophils. The number of participants with neutrophil engraftment was assessed.
Time Frame Day +180 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
Number of participants with neutrophil engraftment was assessed using the Safety Analysis Set.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 181 174
Measure Type: Count of Participants
Unit of Measure: Participants
156
  86.2%
162
  93.1%
37.Secondary Outcome
Title Number of Participants With Platelet Engraftment by Day +180 Post-Hematopoietic Stem Cell Transplant (HSCT)
Hide Description The date of platelet engraftment was recorded on the electronic case report form (eCRF) and is defined as the first date after HSCT of a platelet count >20 x 10^9/L without a platelet transfusion in the preceding seven days. The number of participants with platelet engraftment was assessed.
Time Frame Day +180 Post-HSCT
Hide Outcome Measure Data
Hide Analysis Population Description
Number of Participants with platelet engraftment was assessed using the Safety Analysis Set.
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description:
Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT.
Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
Overall Number of Participants Analyzed 181 174
Measure Type: Count of Participants
Unit of Measure: Participants
154
  85.1%
163
  93.7%
Time Frame Adverse Events (AEs) were reported from the date of consent through Day +180 post-HSCT/Study Completion or Early Termination, or up to 4 years, 1 month.
Adverse Event Reporting Description A treatment-emergent adverse event was defined as any event with onset date on or after the first dose of study treatment or any ongoing event that worsens in severity after the date of the first dose of the study treatment through the protocol-specific reporting period. Only serious adverse events considered by the investigator to be possibly related to study drug were reported more than 30 days after the last dose of the study drug. Adverse Events were assessed with the safety analysis set.
 
Arm/Group Title Defibrotide Prophylaxis Best Supportive Care
Hide Arm/Group Description Defibrotide was administered intravenously at a dose of 6.25mg/kg/day in 4 divided doses by IV infusion over 2 hours in addition to best supportive care within 24 hours before the first dose of the conditioning regimen and continued (for those participants without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post-HSCT. Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and participant need, was administered on the first day of conditioning and continued until Day +30 post HSCT or hospital discharge, whichever was sooner, or diagnosis of VOD, if applicable.
All-Cause Mortality
Defibrotide Prophylaxis Best Supportive Care
Affected / at Risk (%) Affected / at Risk (%)
Total   35/181 (19.34%)      29/174 (16.67%)    
Hide Serious Adverse Events
Defibrotide Prophylaxis Best Supportive Care
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   82/181 (45.30%)      74/174 (42.53%)    
Blood and lymphatic system disorders     
Disseminated intravascular coagulation  1  1/181 (0.55%)  0/174 (0.00%) 
Febrile neutropenia  1  3/181 (1.66%)  3/174 (1.72%) 
Histiocytosis haematophagic  1  3/181 (1.66%)  0/174 (0.00%) 
Thrombocytopenia  1  1/181 (0.55%)  0/174 (0.00%) 
Thrombotic microangiopathy  1  2/181 (1.10%)  3/174 (1.72%) 
Cardiac disorders     
Cardiac arrest  1  1/181 (0.55%)  1/174 (0.57%) 
Cardiac failure  1  1/181 (0.55%)  0/174 (0.00%) 
Cardio-respiratory arrest  1  1/181 (0.55%)  0/174 (0.00%) 
Pericardial effusion  1  1/181 (0.55%)  0/174 (0.00%) 
Sinus tachycardia  1  0/181 (0.00%)  1/174 (0.57%) 
Gastrointestinal disorders     
Abdominal pain  1  1/181 (0.55%)  0/174 (0.00%) 
Anal inflammation  1  1/181 (0.55%)  1/174 (0.57%) 
Colitis  1  1/181 (0.55%)  0/174 (0.00%) 
Diarrhoea  1  0/181 (0.00%)  5/174 (2.87%) 
Enteritis  1  1/181 (0.55%)  1/174 (0.57%) 
Gastrointestinal haemorrhage  1  3/181 (1.66%)  0/174 (0.00%) 
Haematemesis  1  2/181 (1.10%)  0/174 (0.00%) 
Haematochezia  1  1/181 (0.55%)  1/174 (0.57%) 
Lower gastrointestinal haemorrhage  1  1/181 (0.55%)  0/174 (0.00%) 
Melaena  1  1/181 (0.55%)  0/174 (0.00%) 
Nausea  1  1/181 (0.55%)  1/174 (0.57%) 
Pancreatitis  1  0/181 (0.00%)  1/174 (0.57%) 
Pneumatosis intestinalis  1  0/181 (0.00%)  1/174 (0.57%) 
Stomatitis  1  1/181 (0.55%)  3/174 (1.72%) 
Vomiting  1  0/181 (0.00%)  1/174 (0.57%) 
Gait disturbance  1  1/181 (0.55%)  0/174 (0.00%) 
General physical health deterioration  1  0/181 (0.00%)  1/174 (0.57%) 
Influenza like illness  1  0/181 (0.00%)  1/174 (0.57%) 
Mucosal haemorrhage  1  1/181 (0.55%)  0/174 (0.00%) 
Multiple organ dysfunction syndrome  1  3/181 (1.66%)  2/174 (1.15%) 
Pneumatosis  1  0/181 (0.00%)  1/174 (0.57%) 
Pyrexia  1  10/181 (5.52%)  14/174 (8.05%) 
Hepatobiliary disorders     
Cholecystitis acute  1  1/181 (0.55%)  0/174 (0.00%) 
Hepatic failure  1  0/181 (0.00%)  1/174 (0.57%) 
Venoocclusive liver disease  1  2/181 (1.10%)  4/174 (2.30%) 
Immune system disorders     
Acute graft versus host disease in intestine  1  3/181 (1.66%)  4/174 (2.30%) 
Acute graft versus host disease in liver  1  0/181 (0.00%)  1/174 (0.57%) 
Acute graft versus host disease in skin  1  4/181 (2.21%)  1/174 (0.57%) 
Anaphylactic reaction  1  1/181 (0.55%)  0/174 (0.00%) 
Cytokine release syndrome  1  1/181 (0.55%)  0/174 (0.00%) 
Infections and infestations     
Adenovirus infection  1  1/181 (0.55%)  2/174 (1.15%) 
BK virus infection  1  2/181 (1.10%)  0/174 (0.00%) 
Bacterial infection  1  1/181 (0.55%)  0/174 (0.00%) 
Bronchopulmonary aspergillosis  1  1/181 (0.55%)  0/174 (0.00%) 
Candida sepsis  1  1/181 (0.55%)  0/174 (0.00%) 
Cellulitis of male external genital organ  1  1/181 (0.55%)  0/174 (0.00%) 
Clostridium difficile colitis  1  1/181 (0.55%)  0/174 (0.00%) 
Croup infectious  1  1/181 (0.55%)  0/174 (0.00%) 
Cystitis viral  1  1/181 (0.55%)  1/174 (0.57%) 
Cytomegalovirus colitis  1  0/181 (0.00%)  1/174 (0.57%) 
Cytomegalovirus infection  1  2/181 (1.10%)  2/174 (1.15%) 
Cytomegalovirus viraemia  1  0/181 (0.00%)  1/174 (0.57%) 
Device related infection  1  2/181 (1.10%)  3/174 (1.72%) 
Device related sepsis  1  0/181 (0.00%)  1/174 (0.57%) 
Epstein-Barr virus infection  1  0/181 (0.00%)  1/174 (0.57%) 
Herpes zoster  1  1/181 (0.55%)  0/174 (0.00%) 
Infection  1  1/181 (0.55%)  0/174 (0.00%) 
Klebsiella sepsis  1  1/181 (0.55%)  0/174 (0.00%) 
Meningitis  1  0/181 (0.00%)  1/174 (0.57%) 
Meningoencephalitis herpetic  1  0/181 (0.00%)  1/174 (0.57%) 
Pneumonia  1  0/181 (0.00%)  4/174 (2.30%) 
Pseudomonal sepsis  1  1/181 (0.55%)  0/174 (0.00%) 
Respiratory tract infection  1  1/181 (0.55%)  0/174 (0.00%) 
Sepsis  1  6/181 (3.31%)  5/174 (2.87%) 
Septic shock  1  2/181 (1.10%)  0/174 (0.00%) 
Skin candida  1  0/181 (0.00%)  1/174 (0.57%) 
Skin infection  1  1/181 (0.55%)  0/174 (0.00%) 
Staphylococcal bacteraemia  1  1/181 (0.55%)  1/174 (0.57%) 
Staphylococcal sepsis  1  1/181 (0.55%)  0/174 (0.00%) 
Staphylococcal skin infection  1  0/181 (0.00%)  1/174 (0.57%) 
Subcutaneous abscess  1  0/181 (0.00%)  1/174 (0.57%) 
Injury, poisoning and procedural complications     
Airway complication of anaesthesia  1  0/181 (0.00%)  1/174 (0.57%) 
Deep vein thrombosis postoperative  1  0/181 (0.00%)  1/174 (0.57%) 
Delayed engraftment  1  0/181 (0.00%)  1/174 (0.57%) 
Engraft failure  1  1/181 (0.55%)  0/174 (0.00%) 
Subarachnoid haemorrhage  1  1/181 (0.55%)  0/174 (0.00%) 
Subcutaneous haematoma  1  0/181 (0.00%)  1/174 (0.57%) 
Transplant failure  1  0/181 (0.00%)  1/174 (0.57%) 
Traumatic haematoma  1  1/181 (0.55%)  0/174 (0.00%) 
Vascular access complication  1  0/181 (0.00%)  1/174 (0.57%) 
Investigations     
Alanine aminotransferase increased  1  0/181 (0.00%)  1/174 (0.57%) 
Blood bilirubin increased  1  1/181 (0.55%)  2/174 (1.15%) 
Blood creatinine increased  1  1/181 (0.55%)  0/174 (0.00%) 
Cytomegalovirus test positive  1  1/181 (0.55%)  1/174 (0.57%) 
Electrocardiogram QT prolonged  1  1/181 (0.55%)  0/174 (0.00%) 
Epstein-Barr virus test positive  1  1/181 (0.55%)  0/174 (0.00%) 
Klebsiella test positive  1  1/181 (0.55%)  0/174 (0.00%) 
Neutrophil count decreased  1  1/181 (0.55%)  1/174 (0.57%) 
Norovirus test positive  1  0/181 (0.00%)  1/174 (0.57%) 
Weight decreased  1  1/181 (0.55%)  0/174 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite  1  1/181 (0.55%)  0/174 (0.00%) 
Dehydration  1  0/181 (0.00%)  1/174 (0.57%) 
Hypercalcaemia  1  0/181 (0.00%)  2/174 (1.15%) 
Hyperglycaemia  1  2/181 (1.10%)  0/174 (0.00%) 
Hyperkalaemia  1  1/181 (0.55%)  0/174 (0.00%) 
Hypokalaemia  1  2/181 (1.10%)  0/174 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute leukaemia  1  1/181 (0.55%)  0/174 (0.00%) 
Acute lymphocytic leukaemia recurrent  1  1/181 (0.55%)  1/174 (0.57%) 
Acute myeloid leukaemia recurrent  1  1/181 (0.55%)  1/174 (0.57%) 
Burkitt's lymphoma  1  0/181 (0.00%)  1/174 (0.57%) 
Leukaemia  1  0/181 (0.00%)  1/174 (0.57%) 
Leukaemia recurrent  1  0/181 (0.00%)  1/174 (0.57%) 
Nervous system disorders     
Cerebellar haemorrhage  1  0/181 (0.00%)  1/174 (0.57%) 
Cerebral haemorrhage  1  1/181 (0.55%)  1/174 (0.57%) 
Encephalopathy  1  1/181 (0.55%)  0/174 (0.00%) 
Haemorrhage intracranial  1  1/181 (0.55%)  0/174 (0.00%) 
Headache  1  0/181 (0.00%)  1/174 (0.57%) 
Leukoencephalopathy  1  1/181 (0.55%)  0/174 (0.00%) 
Nervous system disorder  1  0/181 (0.00%)  1/174 (0.57%) 
Neuralgia  1  1/181 (0.55%)  0/174 (0.00%) 
Posterior reversible encephalopathy syndrome  1  1/181 (0.55%)  0/174 (0.00%) 
Presyncope  1  1/181 (0.55%)  0/174 (0.00%) 
Seizure  1  0/181 (0.00%)  1/174 (0.57%) 
Renal and urinary disorders     
Acute kidney injury  1  3/181 (1.66%)  4/174 (2.30%) 
Anuria  1  0/181 (0.00%)  1/174 (0.57%) 
Cystitis haemorrhagic  1  1/181 (0.55%)  0/174 (0.00%) 
Nephropathy  1  1/181 (0.55%)  0/174 (0.00%) 
Nephropathy toxic  1  0/181 (0.00%)  1/174 (0.57%) 
Renal failure  1  2/181 (1.10%)  1/174 (0.57%) 
Renal impairment  1  1/181 (0.55%)  0/174 (0.00%) 
Renal injury  1  0/181 (0.00%)  1/174 (0.57%) 
Renal tubular dysfunction  1  1/181 (0.55%)  0/174 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute pulmonary oedema  1  0/181 (0.00%)  1/174 (0.57%) 
Acute respiratory distress syndrome  1  1/181 (0.55%)  1/174 (0.57%) 
Acute respiratory failure  1  1/181 (0.55%)  0/174 (0.00%) 
Dyspnoea  1  1/181 (0.55%)  0/174 (0.00%) 
Epistaxis  1  1/181 (0.55%)  1/174 (0.57%) 
Hypoxia  1  4/181 (2.21%)  0/174 (0.00%) 
Idiopathic pneumonia syndrome  1  1/181 (0.55%)  0/174 (0.00%) 
Laryngospasm  1  1/181 (0.55%)  0/174 (0.00%) 
Organising pneumonia  1  0/181 (0.00%)  1/174 (0.57%) 
Pharyngeal inflammation  1  0/181 (0.00%)  1/174 (0.57%) 
Pleural effusion  1  1/181 (0.55%)  0/174 (0.00%) 
Pulmonary alveolar haemorrhage  1  1/181 (0.55%)  0/174 (0.00%) 
Pulmonary embolism  1  0/181 (0.00%)  1/174 (0.57%) 
Pulmonary haemorrhage  1  0/181 (0.00%)  1/174 (0.57%) 
Pulmonary oedema  1  1/181 (0.55%)  0/174 (0.00%) 
Respiratory distress  1  1/181 (0.55%)  3/174 (1.72%) 
Respiratory failure  1  6/181 (3.31%)  6/174 (3.45%) 
Respiratory tract haemorrhage  1  1/181 (0.55%)  0/174 (0.00%) 
Stridor  1  0/181 (0.00%)  1/174 (0.57%) 
Tachypnoea  1  1/181 (0.55%)  0/174 (0.00%) 
Upper airway obstruction  1  0/181 (0.00%)  1/174 (0.57%) 
Pulmonary arterial hypertension  1  0/181 (0.00%)  1/174 (0.57%) 
Vascular disorders     
Air embolism  1  0/181 (0.00%)  1/174 (0.57%) 
Capillary leak syndrome  1  1/181 (0.55%)  0/174 (0.00%) 
Hypertension  1  0/181 (0.00%)  1/174 (0.57%) 
Hypotension  1  3/181 (1.66%)  2/174 (1.15%) 
Hypovolaemic shock  1  0/181 (0.00%)  1/174 (0.57%) 
Shock  1  0/181 (0.00%)  1/174 (0.57%) 
Venoocclusive disease  1  9/181 (4.97%)  5/174 (2.87%) 
1
Term from vocabulary, MedDRA 19.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Defibrotide Prophylaxis Best Supportive Care
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   180/181 (99.45%)      174/174 (100.00%)    
Blood and lymphatic system disorders     
Anaemia  1  50/181 (27.62%)  163 52/174 (29.89%)  158
Febrile neutropenia  1  52/181 (28.73%)  57 59/174 (33.91%)  70
Leukopenia  1  5/181 (2.76%)  9 10/174 (5.75%)  22
Neutropenia  1  31/181 (17.13%)  52 27/174 (15.52%)  44
Thrombocytopenia  1  31/181 (17.13%)  56 27/174 (15.52%)  77
Cardiac disorders     
Sinus tachycardia  1  37/181 (20.44%)  47 24/174 (13.79%)  30
Gastrointestinal disorders     
Abdominal distension  1  17/181 (9.39%)  21 4/174 (2.30%)  4
Abdominal pain  1  57/181 (31.49%)  87 48/174 (27.59%)  70
Abdominal pain upper  1  12/181 (6.63%)  16 11/174 (6.32%)  11
Constipation  1  40/181 (22.10%)  44 39/174 (22.41%)  40
Diarrhoea  1  110/181 (60.77%)  176 108/174 (62.07%)  178
Haemorrhoids  1  12/181 (6.63%)  14 13/174 (7.47%)  15
Nausea  1  109/181 (60.22%)  166 101/174 (58.05%)  149
Oral pain  1  13/181 (7.18%)  14 8/174 (4.60%)  10
Proctalgia  1  7/181 (3.87%)  8 9/174 (5.17%)  11
Stomatitis  1  105/181 (58.01%)  167 114/174 (65.52%)  188
Vomiting  1  106/181 (58.56%)  208 91/174 (52.30%)  179
General disorders     
Asthenia  1  10/181 (5.52%)  11 7/174 (4.02%)  7
Chills  1  11/181 (6.08%)  16 14/174 (8.05%)  16
Face oedema  1  10/181 (5.52%)  10 12/174 (6.90%)  16
Fatigue  1  24/181 (13.26%)  35 23/174 (13.22%)  28
Malaise  1  7/181 (3.87%)  12 11/174 (6.32%)  16
Oedema peripheral  1  27/181 (14.92%)  33 30/174 (17.24%)  38
Pain  1  22/181 (12.15%)  24 19/174 (10.92%)  20
Pyrexia  1  113/181 (62.43%)  201 113/174 (64.94%)  202
Immune system disorders     
Acute graft versus host disease in intestine  1  13/181 (7.18%)  15 19/174 (10.92%)  19
Acute graft versus host disease in skin  1  31/181 (17.13%)  39 34/174 (19.54%)  41
Engraftment syndrome  1  14/181 (7.73%)  14 15/174 (8.62%)  15
Infections and infestations     
Cytomegalovirus infection  1  26/181 (14.36%)  29 23/174 (13.22%)  24
Cytomegalovirus viraemia  1  6/181 (3.31%)  7 9/174 (5.17%)  9
Device related infection  1  15/181 (8.29%)  17 9/174 (5.17%)  9
Injury, poisoning and procedural complications     
Infusion related reaction  1  15/181 (8.29%)  20 12/174 (6.90%)  16
Investigations     
Activated partial thromboplastin time prolonged  1  17/181 (9.39%)  33 13/174 (7.47%)  33
Alanine aminotransferase increased  1  18/181 (9.94%)  31 28/174 (16.09%)  48
Aspartate aminotransferase increased  1  15/181 (8.29%)  31 28/174 (16.09%)  50
Blood bilirubin increased  1  26/181 (14.36%)  61 20/174 (11.49%)  36
Blood creatinine increased  1  10/181 (5.52%)  25 11/174 (6.32%)  16
Cytomegalovirus test positive  1  16/181 (8.84%)  19 9/174 (5.17%)  15
International normalised ratio increased  1  10/181 (5.52%)  22 12/174 (6.90%)  16
Lymphocyte count decreased  1  6/181 (3.31%)  13 10/174 (5.75%)  24
Neutrophil count decreased  1  19/181 (10.50%)  42 25/174 (14.37%)  74
Platelet count decreased  1  34/181 (18.78%)  168 43/174 (24.71%)  161
Weight decreased  1  22/181 (12.15%)  33 17/174 (9.77%)  21
White blood cell count decreased  1  22/181 (12.15%)  41 17/174 (9.77%)  68
Metabolism and nutrition disorders     
Decreased appetite  1  51/181 (28.18%)  75 51/174 (29.31%)  72
Fluid overload  1  13/181 (7.18%)  16 8/174 (4.60%)  12
Fluid retention  1  14/181 (7.73%)  15 16/174 (9.20%)  18
Hyperglycaemia  1  22/181 (12.15%)  31 17/174 (9.77%)  35
Hyperkalaemia  1  12/181 (6.63%)  16 12/174 (6.90%)  18
Hypoalbuminaemia  1  29/181 (16.02%)  60 23/174 (13.22%)  55
Hypocalcaemia  1  19/181 (10.50%)  28 24/174 (13.79%)  48
Hypokalaemia  1  75/181 (41.44%)  114 63/174 (36.21%)  111
Hypomagnesaemia  1  71/181 (39.23%)  123 59/174 (33.91%)  123
Hyponatraemia  1  17/181 (9.39%)  24 13/174 (7.47%)  19
Hypophosphataemia  1  20/181 (11.05%)  34 23/174 (13.22%)  40
Musculoskeletal and connective tissue disorders     
Arthralgia  1  6/181 (3.31%)  9 10/174 (5.75%)  11
Back pain  1  18/181 (9.94%)  20 8/174 (4.60%)  8
Pain in extremity  1  19/181 (10.50%)  25 15/174 (8.62%)  18
Nervous system disorders     
Headache  1  50/181 (27.62%)  77 36/174 (20.69%)  60
Psychiatric disorders     
Anxiety  1  14/181 (7.73%)  14 19/174 (10.92%)  20
Depression  1  11/181 (6.08%)  11 3/174 (1.72%)  4
Insomnia  1  17/181 (9.39%)  19 31/174 (17.82%)  35
Renal and urinary disorders     
Acute kidney injury  1  8/181 (4.42%)  11 14/174 (8.05%)  18
Haematuria  1  21/181 (11.60%)  23 13/174 (7.47%)  17
Respiratory, thoracic and mediastinal disorders     
Cough  1  24/181 (13.26%)  29 23/174 (13.22%)  26
Dyspnoea  1  12/181 (6.63%)  15 11/174 (6.32%)  11
Epistaxis  1  41/181 (22.65%)  52 46/174 (26.44%)  68
Hypoxia  1  13/181 (7.18%)  15 10/174 (5.75%)  10
Nasal congestion  1  10/181 (5.52%)  13 4/174 (2.30%)  4
Oropharyngeal pain  1  20/181 (11.05%)  21 20/174 (11.49%)  26
Pleural effusion  1  15/181 (8.29%)  16 7/174 (4.02%)  9
Tachypnoea  1  10/181 (5.52%)  10 8/174 (4.60%)  8
Skin and subcutaneous tissue disorders     
Dry skin  1  21/181 (11.60%)  26 11/174 (6.32%)  13
Erythema  1  13/181 (7.18%)  15 14/174 (8.05%)  16
Pruritus  1  13/181 (7.18%)  14 24/174 (13.79%)  26
Pruritus generalised  1  13/181 (7.18%)  17 11/174 (6.32%)  13
Rash  1  32/181 (17.68%)  43 20/174 (11.49%)  26
Rash generalised  1  12/181 (6.63%)  13 6/174 (3.45%)  8
Rash maculo-papular  1  13/181 (7.18%)  15 12/174 (6.90%)  16
Vascular disorders     
Hypertension  1  71/181 (39.23%)  92 55/174 (31.61%)  80
Hypotension  1  28/181 (15.47%)  30 26/174 (14.94%)  32
Venoocclusive disease  1  8/181 (4.42%)  8 20/174 (11.49%)  21
1
Term from vocabulary, MedDRA 19.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Director, Disclosure & Transparency
Organization: Jazz Pharmaceuticals
Phone: 215-870-9177
EMail: ClinicalTrialDisclosure@JazzPharma.com
Layout table for additonal information
Responsible Party: Jazz Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02851407    
Other Study ID Numbers: 15-007
First Submitted: July 27, 2016
First Posted: August 1, 2016
Results First Submitted: October 20, 2021
Results First Posted: March 2, 2022
Last Update Posted: March 2, 2022